Biodegradable Iodinated Polymeric Nanoparticle as Computed Tomography Contrast Agent for Direct Imaging of Cerebral Thrombus

Here, we developed a biodegradable iodinated polymeric nanoparticle for direct imaging of arterial and cerebral thrombi. Bis(2-hydroxyethyl) 5-amino-2,4,6-triiodoisophthalate (HEATI), a high-iodine-content monomer, was polymerized with oxalyl chloride to form ROS-responsive IP-HEATI containing peroxalate linkages. Because ROS are abundant in thrombotic microenvironments, IP-HEATI was designed to undergo time-dependent degradation after imaging. The polymer was encapsulated into glycol chitosan–coated nanoparticles by nanoprecipitation, producing GC@IP-HEATI with a size of 197.2 ± 64.0 nm and a zeta potential of +24.8 mV. Conjugation of a fibrin-targeting peptide yielded Fib-GC@IP-HEATI.
In mouse carotid artery thrombosis models, Fib-GC@IP-HEATI enabled complete thrombus visualization within 30 min after intravenous injection, comparable to fibrin-targeted gold nanoparticles. Its CT-visible thrombus volume decreased by approximately 70% within 24 h, whereas gold nanoparticle contrast persisted, supporting signal loss through nanoparticle degradation. Fib-GC@IP-HEATI also visualized embolic cerebral thrombi in a mouse stroke model, and CT signals co-localized with ex vivo near-infrared fluorescence from labeled clots.
These results demonstrate a biodegradable organic CT contrast agent that combines high iodine loading, fibrin targeting, and ROS-responsive degradation for direct and quantitative cerebral thrombus imaging.